U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

KMT2D lysine methyltransferase 2D [ Homo sapiens (human) ]

Gene ID: 8085, updated on 11-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
KMT2Dprovided by HGNC
Official Full Name
lysine methyltransferase 2Dprovided by HGNC
Primary source
HGNC:HGNC:7133
See related
Ensembl:ENSG00000167548 MIM:602113; AllianceGenome:HGNC:7133
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ALR; KMS; MLL2; MLL4; AAD10; BCAHH; KABUK1; TNRC21; CAGL114
Summary
The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]
Expression
Ubiquitous expression in bone marrow (RPKM 10.0), skin (RPKM 5.8) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See KMT2D in Genome Data Viewer
Location:
12q13.12
Exon count:
55
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (49018978..49060794, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (48981150..49022967, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (49412761..49454577, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 4123 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4419 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4420 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6301 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4421 Neighboring gene Sharpr-MPRA regulatory region 2140 Neighboring gene Sharpr-MPRA regulatory region 4008 Neighboring gene DDN and PRKAG1 antisense RNA 1 Neighboring gene dendrin Neighboring gene protein kinase AMP-activated non-catalytic subunit gamma 1 Neighboring gene Sharpr-MPRA regulatory region 4712 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:49411600-49412190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6302 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:49442744-49443943 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:49443977-49444477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4422 Neighboring gene Sharpr-MPRA regulatory region 5975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4423 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6304 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4424 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6305 Neighboring gene RHEB like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6306 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6307 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:49485416-49485598 Neighboring gene uncharacterized LOC105369759 Neighboring gene GATA motif-containing MPRA enhancer 293 Neighboring gene desert hedgehog signaling molecule

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Characterizing the molecular impact of KMT2D variants on the epigenetic and transcriptional landscapes in Kabuki syndrome. Jung YL, et al. Hum Mol Genet, 2023 Jun 19. PMID 37043208
  2. Histone methyltransferase KMT2D promotes prostate cancer progression through paracrine IL-6 signaling. Zhang J, et al. Biochem Biophys Res Commun, 2023 May 7. PMID 36924677
  3. KMT2D Regulates the NCOA6/THRB Signal Axis through Epigenetic Modification to Promote the Migration and Invasion of Papillary Thyroid Cancer. Wang R, et al. Front Biosci (Landmark Ed), 2023 Jan 18. PMID 36722273
  4. Mutational Landscape of Bladder Cancer in Mexican Patients: KMT2D Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion. Pérez-Montiel MD, et al. Int J Mol Sci, 2023 Jan 6. PMID 36674608, Free PMC Article
  5. Pan-Cancer Analysis of Histone Methyltransferase KMT2D with Potential Implications for Prognosis and Immunotherapy in Human Cancer. Chen G, et al. Comb Chem High Throughput Screen, 2023. PMID 35189794

See all (240) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
    Title: KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
  2. Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
    Title: Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
  3. EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
    Title: EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
  4. SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder.
    Title: SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder.
  5. Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1.
    Title: Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1.
  6. [Two novel and de novo KMT2D mutations on the same allele cause Kabuki syndrome].
    Title: [Two novel and de novo KMT2D mutations on the same allele cause Kabuki syndrome].
  7. Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer.
    Title: Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer.
  8. KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.
    Title: KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.
  9. MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.
    Title: MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.
  10. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression.
    Title: The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression.
Submit: New GeneRIF Correction See all GeneRIFs (163)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-01-23)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-23)

ClinGen Genome Curation PagePubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding NAS
Non-traceable Author Statement
more info
 PubMed 
enables histone H3K4 methyltransferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables histone H3K4 methyltransferase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables histone H3K4 methyltransferase activity TAS
Traceable Author Statement
more info
  
enables histone H3K4 monomethyltransferase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3K4 trimethyltransferase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transcription cis-regulatory region binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription coactivator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in beta-catenin-TCF complex assembly TAS
Traceable Author Statement
more info
  
involved_in heterochromatin formation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in methylation IEA
Inferred from Electronic Annotation
more info
  
involved_in oocyte growth ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in oogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of intracellular estrogen receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of DNA-templated transcription NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to estrogen IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of MLL3/4 complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of MLL3/4 complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of MLL3/4 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

Go to the top of the page Help
Preferred Names
histone-lysine N-methyltransferase 2D
Names
ALL1-related protein
Kabuki make-up syndrome
histone-lysine N-methyltransferase MLL2
lysine (K)-specific methyltransferase 2D
lysine N-methyltransferase 2D
myeloid/lymphoid or mixed-lineage leukemia 2
trinucleotide repeat containing 21
NP_003473.3

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_027827.1 RefSeqGene

    Range
    5001..41350
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_003482.4 → NP_003473.3  histone-lysine N-methyltransferase 2D

    See identical proteins and their annotated locations for NP_003473.3

    Status: REVIEWED

    Source sequence(s)
    AC011603
    Consensus CDS
    CCDS44873.1
    UniProtKB/Swiss-Prot
    O14686, O14687
    UniProtKB/TrEMBL
    A0A8I5KSG1
    Related
    ENSP00000301067.7, ENST00000301067.12
    Conserved Domains (11) summary
    smart00398
    Location:2021 → 2072
    HMG; high mobility group
    smart00542
    Location:5240 → 5327
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:5397 → 5519
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    cd15509
    Location:228 → 273
    PHD1_KMT2C_like; PHD finger 1 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D)
    cd15513
    Location:1429 → 1475
    PHD5_KMT2C_like; PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D
    cd15597
    Location:1378 → 1428
    PHD3_KMT2D; PHD finger 3 found in Histone-lysine N-methyltransferase 2D (KMT2D)
    cd15601
    Location:1506 → 1556
    PHD5_KMT2D; PHD finger 5 found in Histone-lysine N-methyltransferase 2D (KMT2D)
    cd15695
    Location:134 → 217
    ePHD1_KMT2D; Extended PHD finger 1 found in histone-lysine N-methyltransferase 2D (KMT2D)
    cd15698
    Location:5032 → 5138
    ePHD2_KMT2D; Extended PHD finger 2 found in histone-lysine N-methyltransferase 2D (KMT2D)
    pfam05964
    Location:5182 → 5232
    FYRN; F/Y-rich N-terminus
    cl22851
    Location:275 → 320
    PHD_SF; PHD finger superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    49018978..49060794 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    48981150..49022967 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O14686.2 GenPept UniProtKB/Swiss-Prot:O14686

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous